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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:ZNF561-MED16

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZNF561-MED16
FusionPDB ID: 102372
FusionGDB2.0 ID: 102372
HgeneTgene
Gene symbol

ZNF561

MED16

Gene ID

93134

10025

Gene namezinc finger protein 561mediator complex subunit 16
Synonyms-DRIP92|THRAP5|TRAP95
Cytomap

19p13.2

19p13.3

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 561mediator of RNA polymerase II transcription subunit 16thyroid hormone receptor-associated protein 5thyroid hormone receptor-associated protein complex 95 kDa componentthyroid hormone receptor-associated protein, 95-kD subunitvitamin D3 receptor-intera
Modification date2020031320200313
UniProtAcc.

Q9Y2X0

Main function of 5'-partner protein: FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. {ECO:0000269|PubMed:10198638, ECO:0000269|PubMed:10235266}.
Ensembl transtripts involved in fusion geneENST idsENST00000302851, ENST00000326044, 
ENST00000424629, ENST00000354661, 
ENST00000495503, 
ENST00000606828, 
ENST00000269814, ENST00000312090, 
ENST00000325464, ENST00000395808, 
ENST00000589119, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=88 X 8 X 6=384
# samples 29
** MAII scorelog2(2/8*10)=1.32192809488736log2(9/384*10)=-2.09310940439148
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZNF561 [Title/Abstract] AND MED16 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZNF561 [Title/Abstract] AND MED16 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZNF561(9727721)-MED16(871253), # samples:2
Anticipated loss of major functional domain due to fusion event.ZNF561-MED16 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
ZNF561-MED16 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
ZNF561-MED16 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
ZNF561-MED16 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ZNF561-MED16 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
TgeneMED16

GO:0006367

transcription initiation from RNA polymerase II promoter

12218053

TgeneMED16

GO:0045893

positive regulation of transcription, DNA-templated

10198638



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:9727721/chr19:871253)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across ZNF561 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across MED16 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000302851ZNF561chr199727721-ENST00000269814MED16chr19871253-14426053161032238
ENST00000326044ZNF561chr199727721-ENST00000269814MED16chr19871253-1273436147863238

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000302851ENST00000269814ZNF561chr199727721-MED16chr19871253-0.0418443640.9581556
ENST00000326044ENST00000269814ZNF561chr199727721-MED16chr19871253-0.0394876750.9605124

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for ZNF561-MED16

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZNF561chr199727721MED16chr1987125343694YRDVMLENYMNLASVGRDEGPASEPD
ZNF561chr199727721MED16chr1987125360594YRDVMLENYMNLASVGRDEGPASEPD

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Potential FusionNeoAntigen Information of ZNF561-MED16 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
ZNF561-MED16_9727721_871253.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
ZNF561-MED16chr199727721chr19871253605HLA-A31:02YMNLASVGR0.9130.6216817
ZNF561-MED16chr199727721chr19871253605HLA-B51:07ENYMNLASV0.59810.6123615

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Potential FusionNeoAntigen Information of ZNF561-MED16 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
ZNF561-MED16_9727721_871253.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
ZNF561-MED16chr199727721chr19871253605DRB1-1183YMNLASVGRDEGPAS823
ZNF561-MED16chr199727721chr19871253605DRB1-1501DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1506DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1509DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1513DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1516DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1518DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1520DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1522DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1524DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1528DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1532DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1533DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1535DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1536DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1537DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1540DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1541DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1542DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1543DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1545DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB1-1546DVMLENYMNLASVGR217
ZNF561-MED16chr199727721chr19871253605DRB5-0101LENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0101MLENYMNLASVGRDE419
ZNF561-MED16chr199727721chr19871253605DRB5-0101ENYMNLASVGRDEGP621
ZNF561-MED16chr199727721chr19871253605DRB5-0102LENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0102MLENYMNLASVGRDE419
ZNF561-MED16chr199727721chr19871253605DRB5-0102ENYMNLASVGRDEGP621
ZNF561-MED16chr199727721chr19871253605DRB5-0103LENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0103MLENYMNLASVGRDE419
ZNF561-MED16chr199727721chr19871253605DRB5-0103ENYMNLASVGRDEGP621
ZNF561-MED16chr199727721chr19871253605DRB5-0104LENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0104MLENYMNLASVGRDE419
ZNF561-MED16chr199727721chr19871253605DRB5-0104ENYMNLASVGRDEGP621
ZNF561-MED16chr199727721chr19871253605DRB5-0105LENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0105MLENYMNLASVGRDE419
ZNF561-MED16chr199727721chr19871253605DRB5-0105ENYMNLASVGRDEGP621
ZNF561-MED16chr199727721chr19871253605DRB5-0108NLENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0108NMLENYMNLASVGRDE419
ZNF561-MED16chr199727721chr19871253605DRB5-0108NENYMNLASVGRDEGP621
ZNF561-MED16chr199727721chr19871253605DRB5-0111LENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0113LENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0113MLENYMNLASVGRDE419
ZNF561-MED16chr199727721chr19871253605DRB5-0113ENYMNLASVGRDEGP621
ZNF561-MED16chr199727721chr19871253605DRB5-0114LENYMNLASVGRDEG520
ZNF561-MED16chr199727721chr19871253605DRB5-0114MLENYMNLASVGRDE419
ZNF561-MED16chr199727721chr19871253605DRB5-0114ENYMNLASVGRDEGP621
ZNF561-MED16chr199727721chr19871253605DRB5-0203LENYMNLASVGRDEG520

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Fusion breakpoint peptide structures of ZNF561-MED16

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
2002ENYMNLASVGRDEGZNF561MED16chr199727721chr19871253605

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZNF561-MED16

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN2002ENYMNLASVGRDEG-7.9962-8.1096
HLA-B14:023BVN2002ENYMNLASVGRDEG-5.70842-6.74372
HLA-B52:013W392002ENYMNLASVGRDEG-6.83737-6.95077
HLA-B52:013W392002ENYMNLASVGRDEG-4.4836-5.5189
HLA-A11:014UQ22002ENYMNLASVGRDEG-10.0067-10.1201
HLA-A11:014UQ22002ENYMNLASVGRDEG-9.03915-10.0745
HLA-A24:025HGA2002ENYMNLASVGRDEG-6.56204-6.67544
HLA-A24:025HGA2002ENYMNLASVGRDEG-5.42271-6.45801
HLA-B44:053DX82002ENYMNLASVGRDEG-7.85648-8.89178
HLA-B44:053DX82002ENYMNLASVGRDEG-5.3978-5.5112
HLA-A02:016TDR2002ENYMNLASVGRDEG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ZNF561-MED16

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
ZNF561-MED16chr199727721chr19871253615ENYMNLASVACATGAACCTGGCCTCTGTGGGTCGCG
ZNF561-MED16chr199727721chr19871253817YMNLASVGRACCTGGCCTCTGTGGGTCGCGATGAGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ZNF561-MED16chr199727721chr19871253217DVMLENYMNLASVGRTGCTGGAGAACTACATGAACCTGGCCTCTGTGGGTCGCGATGAGG
ZNF561-MED16chr199727721chr19871253419MLENYMNLASVGRDEAGAACTACATGAACCTGGCCTCTGTGGGTCGCGATGAGGGCCCAG
ZNF561-MED16chr199727721chr19871253520LENYMNLASVGRDEGACTACATGAACCTGGCCTCTGTGGGTCGCGATGAGGGCCCAGCGA
ZNF561-MED16chr199727721chr19871253621ENYMNLASVGRDEGPACATGAACCTGGCCTCTGTGGGTCGCGATGAGGGCCCAGCGAGCG
ZNF561-MED16chr199727721chr19871253823YMNLASVGRDEGPASACCTGGCCTCTGTGGGTCGCGATGAGGGCCCAGCGAGCGAGCCGG

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Information of the samples that have these potential fusion neoantigens of ZNF561-MED16

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
OVZNF561-MED16chr199727721ENST00000302851chr19871253ENST00000269814TCGA-13-1409-01A

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Potential target of CAR-T therapy development for ZNF561-MED16

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to ZNF561-MED16

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to ZNF561-MED16

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource